Interferon-gamma-inducing factor elicits antitumor immunity in association with interferon-gamma production.
Interferon-gamma-inducing factor (IGIF) is a novel cytokine that stimulates T-cell proliferation, augments natural killer (NK) cell lytic activity, and induces interferon-gamma (IFN-gamma) production in established type 1 T-helper (Th1) cells in the presence of anti-CD3 antibody. The in vitro induction of IFN-gamma by recombinant murine IGIF in these cells was more potent than that induced by murine interleukin-12 (IL-12) and occurred apparently independent of murine IL-12. Here we report that subcutaneous injection into mice of tumor cells transfected with murine IGIF complementary DNA (cDNA) resulted in > or = 10-fold increase of mitogen-stimulated IFN-gamma production in cultured splenocytes. In addition, IGIF-transfected Renca and K1735 tumor cells can be rejected in vivo. The IGIF antitumor effect was abrogated in mice that were sublethally irradiated or depleted of both CD4+ and CD8+ T cells but not in mice depleted of either subpopulation alone. The antitumor effect mediated by IGIF appears to be dependent on IFN-gamma production, because in vivo neutralization of IFN-gamma was accompanied by growth of IGIF-transfected tumors in 100% of the animals. Taken together, our results show that murine IGIF can elicit T-cell-dependent antitumor immunity associated with IFN-gamma induction.
Tan
J
J
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Crucian
B E
BE
Chang
A E
AE
Aruga
E
E
Aruga
A
A
Dovhey
S E
SE
Tanigawa
K
K
Yu
H
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D015316:Genetic Therapy; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D020382:Interleukin-18; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D020382:Interleukin-18; D011994:Recombinant Proteins; D007371:Interferon-gamma